The goal is this proposal is to understand the effect of a cytoplasmic endosymbiont, Wolbachia sp, a member of the alpha subdivision of the Proteobacteria, on the evolutionary genetics of its host, the flour beetle, Tribolium confusum. Members of the Proteobacteria, taxonomically closely related to Wolbachia, are pathogenic in humans and other mammals. The Wolbachia has several effects on its host: (1) it causes reproductive incompatibility between infected males and noninfected females; (2) its enhances the post-copulatory fertility of infected males when competing with uninfected males; and, (3) it causes a sex ratio bias favoring females in some host populations. All three effects accelerate the rate of spread of the microorganism through the host population. The advantage to the sperm of infected males has important effects on the rate of decay of cyto-nuclear disequilibria and can result in very complex dynamics for disequilibria associated with X-linked host nuclear genes. Sex ratio distortion will further complicate the dynamics. Host populations resistant to the incompatibility effect have been discovered. These populations may be resistant because of genetic changes in the Wolbachia, in the host, or both. Understanding the genetic mechanism of this resistance is one of the key goals of the proposed empirical research. The proposed research will use a combination of theoretical population genetic models and empirical laboratory experiments to further our understanding of genetic and evolutionary effects of such microorganisms on their hosts.